Optimizations of force-field parameters for protein systems with the secondary-structure stability and instability

TL;DR

This paper introduces a new method for refining protein force-field parameters by aligning simulation results with experimental secondary-structure stability, demonstrated through improved peptide folding simulations.

Contribution

The authors developed a novel optimization approach for force-field parameters based on secondary-structure stability agreement, applied it to refine the AMBER ff99SB force field.

Findings

Refined force field better reproduces experimental structures.

Optimized torsion-energy parameters improved folding simulation accuracy.

New parameters yielded structures more consistent with experiments.

Abstract

We propose a novel method for refining force-field parameters of protein systems. In this method, the agreement of the secondary-structure stability and instability between the protein conformations obtained by experiments and those obtained by molecular dynamics simulations is used as a criterion for the optimization of force-field parameters. As an example of the applications of the present method, we refined the force-field parameter set of the AMBER ff99SB force field by searching the torsion-energy parameter spaces of $\psi$ (N-C$^{\alpha}$-C-N) and $\zeta$ (C$^{\beta}$-C$^{\alpha}$-C-N) of the backbone dihedral angles. We then performed folding simulations of $\alpha$-helical and $\beta$-hairpin peptides, using the optimized force field. The results showed that the new force-field parameters gave structures more consistent with the experimental implications than the original AMBER ff99SB force field.